Common AAV gene therapy vectors show indiscriminate transduction of living human brain cell types.

The development of cell-type-specific gene therapy vectors for treating neurological diseases holds great promise, but has relied on animal models with limited translational utility. We have adapted an organotypic model to evaluate adeno-associated virus (AAV) transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

Brain metastasis burden and management in patients with small cell lung cancer in Canada: a retrospective, population-based cohort study.

Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada.

Methods: This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018.

Validation of the Emergency Department Work Index in a Pediatric Freestanding Community Emergency Department.

Objectives: The Emergency Department Work Index (EDWIN) is a validated overcrowding score shown to correlate well with staff assessment of adult emergency department (ED) overcrowding and the potential need for diversion. It derives from the number of staffed ED beds, attending physicians on duty, patients within each triage category, and admitted patients. To date, no study has validated EDWIN in a pediatric community ED setting.

Safe Implantation of a Bovine Bioprosthetic Aortic Valve in a Patient With Galactose-α-1,3-Galactose Allergy.

Allergy to galactose-α-1,3-galactose (alpha-gal) is associated with immediate allergic manifestations and premature degeneration of the prosthesis in patients who receive bovine- or porcine-derived bioprosthetic valves. Here, we report a 72-year-old man with atrial fibrillation, aortic regurgitation, and severe alpha-gal allergy who presented for consideration of aortic valve replacement. He was premedicated with antihistamines and steroids and underwent aortic valve replacement with 25-mm INSPIRIS aortic valve (Edwards Lifesciences) and left atrial appendage occlusion with 40-mm AtriClip device (AtriCure), without immediate or short-term complications.

Organ Donation by the Imminently Dead: Addressing the Organ Shortage and the Dead Donor Rule.

The dead donor rule (DDR) has facilitated the saving of hundreds of thousands of lives. Recent advances in heart donation, however, have exposed how DDR has limited donation of all organs. We propose advancing the moment in the dying process at which death can be determined to increase substantially the supply of organs for transplantation.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

Aim: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022).

Methods: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer.

Clinical Decision Support for Hypertension Management in Chronic Kidney Disease: A Randomized Clinical Trial.

Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death.

Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD.

Design, Setting, And Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022.

Cholinergic Basal Forebrain Connectivity to the Basolateral Amygdala Modulates Food Intake.

Obesity results from excessive caloric input associated with overeating and presents a major public health challenge. The hypothalamus has received significant attention for its role in governing feeding behavior and body weight homeostasis. However, extrahypothalamic brain circuits also regulate appetite and consumption by altering sensory perception, motivation, and reward.

Heart Transplantation for Adults With Congenital Heart Disease Can Be Performed at Adult or Pediatric Hospitals With Comparable Outcomes.

Introduction: The goal of this study was to evaluate the relationship between hospital-related factors and hospital type on outcomes of heart transplantation for patients with adult congenital heart disease (ACHD).

Methods: Patients with ACHD who underwent heart transplant between 2010 and 2021 were identified using the United Network for Organ Sharing data registry. The primary outcome was post-transplant mortality.

Impacts of HO, SARM1 inhibition, and high NAm concentrations on Huntington's disease laser-induced degeneration.

Axonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect.

Coronary Artery Aneurysms, Arteriovenous Malformations, and Spontaneous Dissections-A Review of the Evidence.

Background: Coronary artery aneurysms (CAAs), coronary arteriovenous malformations (CAVMs), and spontaneous coronary artery dissections (SCADs) are rare clinical entities, and much is unknown about their natural history, prognosis, and management.

Methods: A systematic search of MEDLINE, Embase, and Cochrane Library databases was performed in March 2023 to identify published papers related to CAAs, CAVMs, and SCADs.

Results: CAAs are found in 0.

Participant Experience with Protocol Research Kidney Biopsies in the Kidney Precision Medicine Project.

Background: Kidney biopsies are procedures commonly performed in clinical nephrology and are increasingly used in research. In this study, we aimed to evaluate the experiences of participants who underwent research kidney biopsies in the Kidney Precision Medicine Project (KPMP).

Methods: KPMP research participants with AKI or CKD were enrolled at nine recruitment sites in the United States between September 2019 and January 2023.

Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells.

Background: JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections; however, NK-cell response to JCPyV infection remains unexplored.

Methods: NK- and T-cell responses against the JCPyV VP1 were compared using intracellular cytokine staining upon stimulation with peptide pools.

Prevalence of post-liver transplant complications and NASH-related cirrhosis in postmenopausal women.

Introduction And Objectives: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications.

Materials And Methods: Chart review of 1200 LT patients from 2002-2020 was performed.

An evidence-based review of life-threatening secondary headaches in pediatric patients in the emergency department.

Headache is a common complaint in pediatric patients presenting to the emergency department. Diagnosis of life-threatening pathology can be difficult due to the nonspecific symptoms for many of these conditions. Emergency clinicians must have a high index of suspicion, obtain a detailed history, and conduct a thorough physical examination to accurately identify life-threatening causes of headache.

Story telling in bilingual Urdu-Cantonese ethnic minority children: Macrostructure and its relation to microstructural linguistic skills.

Introduction: The ability to produce a well-structured, coherent and informative narrative requires the integration of lexical and grammatical skills at different levels of complexity. Investigating how narrative macrostructure competence is predicted by microstructural linguistic skills is conceptually enlightening; yet there have been very few, if any, studies documenting the associations between macrostructure and microstructure in both languages of the same bilinguals. In this paper we attempt to address this research gap and report on the first empirical study of Urdu-Cantonese bilingual children's narrative abilities, bringing in data from a new language pair that is currently understudied.

The impact of a student-led anti-racism programme on medical students' perceptions and awareness of racial bias in medicine and confidence to advocate against racism.

Introduction: Systemic racism impacts personal and community health; however, education regarding its role in perpetuating healthcare inequity remains limited in medical curricula. This study implemented and evaluated the impact of a student-led anti-racism programme on medical students' perceptions of racial bias in medicine, awareness of, and confidence to advocate against racism in medicine.

Method: A total of 543 early stage medical students were invited to participate in the programme.

IN-HOME-PDCaregivers: The effects of a combined home visit and peer mentoring intervention for caregivers of homebound individuals with advanced Parkinson's disease.

Introduction: Family caregivers of people with advanced Parkinson's Disease (PD) are at high risk of caregiver strain, which independently predicts adverse patient outcomes. We tested the effects of one year of interdisciplinary, telehealth-enhanced home visits (IN-HOME-PD) with 16 weeks of peer mentoring on caregiver strain compared with usual care.

Methods: We enrolled homebound people with advanced PD (PWPD) and their primary caregiver as IN-HOME-PD dyads.

Hip Arthroscopy Results in Similar Short-Term Function Compared to Total Hip Arthroplasty in Patients of Similar Demographic Profiles.

Purpose: To review short-term functional outcomes in patients who underwent hip arthroscopy and to compare their outcomes to those of a demographically similar cohort who underwent total hip arthroplasty (THA).

Methods: Data were prospectively collected and retrospectively reviewed for patients undergoing hip arthroscopy (SCOPE) between April 2008 and October 2015. SCOPE patients were included if they were ≥35 years, had preoperative and postoperative 2-year follow-up, and had no prior hip condition or ipsilateral hip surgery.

How to implement a clinical robotic mitral valve surgery program.

Minimally invasive, specifically, robot-assisted mitral valve surgery has evolved as a method to intervene on mitral valve disease without a median sternotomy while providing the advantages of excellent visualization and allowing for precise technical movements in a small space with the goal to decrease surgical invasiveness, post-operative pain, and hospital length of stay. As patient interest in minimally invasive cardiac procedures become more prevalent and patients seek the opportunity to undergo robotic valve surgery, institutions worldwide are exploring the potential of establishing a robotic mitral valve surgery program. While robust existing experience in open surgical mitral valve repair, careful patient selection, a dedicated team, and institution support are fundamental factors to implement a new robotic mitral valve surgery program, we believe that simulation team training prior to transitioning to live cases is also crucial and should be incorporated to establish a successful mitral valve surgery program.